This project aims to understand the pathophysiology of immunologically mediated lung inflammation and inflammatory lung diseases by analyzing localization and function of T lymphocytes in the lung. It will extend recent observations that the lymphoid cells from the lungs of non-immune mice are hyporesponsive to alloantigen in generating a CTL response, apparently because lung macrophages suppress helper cell function. In alloimmunized mice, both homing, and enhanced immune responsiveness of lung, result in selective accumulation of CTL and other activated T cells in the lung. The project aims to study T cell function in lungs from non-immune mice, and the mechanisms by which lung macrophages regulate T cell function. It will also analyze T cell function in lungs from alloimmune mice, including the mechanisms of enhanced T cell function, the functional characteristics of cell subsets which accumulate in lungs of immune animals, and the effect of immunization with "conventional," soluble or particulate, antigens on lung T cell function. It will assess homing of CTL populations to lungs vs. other lymphoid organs, and to lungs of non-immune vs. immune mice. An additional aim of the grant is to extend studies which have demonstrated that small numbers of human lung macrophages (isolated from surgical specimens) enhanced Con A-induced lymphocyte proliferation, while larger numbers inhibit. Macrophage-derived lysates and supernatants contain enhancing and inhibitory activities; the enhancing activity is, putatively, a newly described monokine. Further studies will analyze the parameters of production of the factors, the heterogeneity of macrophage populations (compared to monocytes) in producing the factors, and the capacity of macrophages from normal individuals to produce the factors. These studies should help define the immunoregulatory control mechanisms in lungs from non-immune animals, the mechanisms by which immunization induces lung T cell activation, and the in vitro significance of potent macrophage- derived T lymphocyte regulatory factors.